The nature of metal binding sites in copper-containing proteins is being probed by chemical modification studies in combination with spectral investigations and by studies of synthetic model systems. The proteins being studied directly are azurin, stellacyanin, and laccase. Apoproteins, metal-replaced, and metal-substituted proteins are being prepared and characterized. In the case of azurin the kinetics of metal uptake by the peptide moiety is being examined in an effort to understand the basis of the kinetic selectivity which is expressed for Cu(II). Attempts to prepare liganded and mixed derivatives of laccase are being pursued to get at cooperative interactions among the metal binding sites. A small molecule system with an N2S2 donor set is being synthesized as a model of the type l site. Kinetic studies of amacrocyclic copper complex are also planned.